Ischemia is the lack of oxygenated blood flow to various body parts and organs. Cerebral ischemia is an ischemic condition where the brain or parts of the brain do not receive enough blood flow to maintain normal neurological function. Cerebral ischemia can be the result of various serious diseases such as stroke and cardiac arrest or the result of arterial obstruction such as strangulation. Severe or prolonged cerebral ischemia results in unconsciousness, brain damage, or death.
Therapeutic hypothermia has been shown to minimize brain injury and improve prognosis after cardiac arrest (CA). Mild therapeutic hypothermia, which involves decreasing core body temperature (Tb) to between 32-34° C. within 2 hr of restoration of spontaneous circulation (ROSC) and maintaining reduced Tb for 12-24 hr, is currently the only clinical intervention available for global cerebral ischemia (Hypothermia-after-Cardiac-Arrest-Study-Group, 2002; Seupaul and Wilbur, 2011). The clinical benefit of mild therapeutic hypothermia following focal cerebral ischemia is less clear (Bi et al., 2011; Faridar et al., 2011), but cooling shows obvious benefits in animal models of ischemic stroke (Busto et al., 1987). The fact that therapeutic hypothermia has not so far shown benefits in stroke trials may stem from failure to achieve Tb's between 32-34° C. (Faridar et al., 2011; Jordan and Carhuapoma, 2007). Shivering is the most problematic issue in achieving and maintaining hypothermia using conventional technology that relies on external or internal cooling mechanisms such as ice packs or i.v. infusion of cold saline. Shivering counteracts efforts to lower Tb and can be exceedingly uncomfortable for awake patients, such as those with a typical ischemic stroke (Sessler, 2009). Using standard pharmacotherapies to suppress shivering, current cooling techniques achieve core body temperature of only 35° C. in patients with acute ischemic stroke (Kollmar et al., 2009) or conscious healthy volunteers (Testori et al., 2011). What is needed are methods and compositions for inducing therapeutic hypothermia to facilitate treating or preventing ischemic brain damage.